Variant 10-17157650-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004412.7(TRDMT1):c.678T>G(p.Asp226Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000572 in 1,613,644 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

TRDMT1
NM_004412.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.496

Variant links:

Genes affected

TRDMT1 (HGNC:2977): (tRNA aspartic acid methyltransferase 1) This gene encodes a protein responsible for the methylation of aspartic acid transfer RNA, specifically at the cytosine-38 residue in the anticodon loop. This enzyme also possesses residual DNA-(cytosine-C5) methyltransferase activity. While similar in sequence and structure to DNA cytosine methyltransferases, this gene is distinct and highly conserved in its function among taxa. [provided by RefSeq, Jun 2010]

TRDMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025156736).

BP6

Variant 10-17157650-A-C is Benign according to our data. Variant chr10-17157650-A-C is described in ClinVar as [Benign]. Clinvar id is 769768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRDMT1	NM_004412.7 link	c.678T>G	p.Asp226Glu	missense_variant	Exon 8 of 11	ENST00000377799.8	NP_004403.1	O14717-1Q6ICS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRDMT1	ENST00000377799.8 link	c.678T>G	p.Asp226Glu	missense_variant	Exon 8 of 11	1	NM_004412.7	ENSP00000367030.3		O14717-1

Frequencies

GnomAD3 genomes

AF:

0.00323

AC:

492

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000724

AC:

181

AN:

250082

Hom.:

AF XY:

0.000540

AC XY:

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000294

AC:

430

AN:

1461330

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

188

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.00324

AC:

493

AN:

152314

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

226

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.00396

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000931

AC:

113

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.4

DANN

Benign

0.96

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.54

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

0.070

N;N

REVEL

Benign

0.044

Sift

Benign

0.70

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.020

MutPred

0.44

Gain of methylation at K225 (P = 0.0901);.;

MVP

0.36

MPC

0.016

ClinPred

0.0024

GERP RS

0.086

Varity_R

0.033

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over